title: Effects of creatine supplementation on muscle wasting and glucose homeostasis in rats treated with dexamethasone.
abstract: We aimed to investigate the possible role of creatine (CR) supplementation in counteracting dexamethasone-induced muscle wasting and insulin resistance in rats. Also, we examined whether CR intake would modulate molecular pathways involved in muscle remodeling and insulin signaling. Animals were randomly divided into four groups: (1) dexamethasone (DEX); (2) control pair-fed (CON-PF); (3) dexamethasone plus CR (DEX-CR); and (4) CR pair-fed (CR-PF). Dexamethasone (5 mg/kg/day) and CR (5 g/kg/day) were given via drinking water for 7 days. Plantaris and extensor digitorum longus (EDL) muscles were removed for analysis. Plantaris and EDL muscle mass were significantly reduced in the DEX-CR and DEX groups when compared with the CON-PF and CR-PF groups (P<0.05). Dexamethasone significantly decreased phospho-Ser473-Akt protein levels compared to the CON-PF group (P<0.05) and CR supplementation aggravated this response (P<0.001). Serum glucose was significantly increased in the DEX group when compared with the CON-PF group (DEX 7.8±0.6 vs. CON-PF 5.2±0.5 mmol/l; P<0.05). CR supplementation significantly exacerbated hyperglycemia in the dexamethasone-treated animals (DEX-CR 15.1±2.4 mmol/l; P<0.05 vs. others). Dexamethasone reduced GLUT-4 translocation when compared with the CON-PF and CR-PF (P<0.05) groups and this response was aggravated by CR supplementation (P<0.05 vs. others). In conclusion, supplementation with CR resulted in increased insulin resistance and did not attenuate muscle wasting in rats treated with dexamethasone. Given the contrast with the results of human studies that have shown benefits of CR supplementation on muscle atrophy and insulin sensitivity, we suggest caution when extrapolating this animal data to human subjects.
authors.affiliation: Laboratory of Applied Nutrition and Metabolism, School of Physical Education and Sports, University of São Paulo, Av. Prof. Mello Moraes, 65, São Paulo, SP, 05508-030, Brazil. nicastro@usp.br
authors.forename: Humberto
authors.initials: H
authors.lastname: Nicastro
authors.forename: Bruno
authors.initials: B
authors.lastname: Gualano
authors.forename: Wilson Max Almeida Monteiro
authors.initials: WM
authors.lastname: de Moraes
authors.forename: Vitor
authors.initials: V
authors.lastname: de Salles Painelli
authors.forename: Claudia Ribeiro
authors.initials: CR
authors.lastname: da Luz
authors.forename: Andre
authors.initials: A
authors.lastname: dos Santos Costa
authors.forename: Fabiana
authors.initials: F
authors.lastname: de Salvi Guimarães
authors.forename: Alessandra
authors.initials: A
authors.lastname: Medeiros
authors.forename: Patricia Chakur
authors.initials: PC
authors.lastname: Brum
authors.forename: Antonio Herbert
authors.initials: AH
authors.lastname: Lancha
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D003401:Creatine / Q000008:administration & dosage*; D003907:Dexamethasone / Q000008:administration & dosage*; D060766:Drinking Water; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D009133:Muscular Atrophy / Q000188:drug therapy / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats
chemical_list: D001786:Blood Glucose; D060766:Drinking Water; D051275:Glucose Transporter Type 4; C495694:Slc2a4 protein, rat; D003907:Dexamethasone; D051057:Proto-Oncogene Proteins c-akt; D003401:Creatine